ASP-Enzymosomes with Saccharomyces cerevisiae Asparaginase II Expressed in Pichia pastoris: Formulation Design and In Vitro Studies of a Potential Antileukemic Drug
| Autor: | M. Bárbara F. Martins, Elba P. S. Bon, M. Luísa Corvo, Surza Lucia Gonçalves da Rocha, Manuela Carvalheiro, Luciana Facchinetti de Castro Girão, Maria Antonieta Ferrara, Margarida Ferreira-Silva, Jonas Perales |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Asparaginase
QH301-705.5 Drug Compounding nanoformulations Antineoplastic Agents Saccharomyces cerevisiae Glutaminase activity Jurkat cells Article Catalysis Pichia pastoris Inorganic Chemistry Jurkat Cells chemistry.chemical_compound ASP3 gene leukemia treatment Acute lymphocytic leukemia ASP-enzymosomes Tumor Cells Cultured medicine Humans Physical and Theoretical Chemistry Biology (General) Molecular Biology QD1-999 Spectroscopy Leukemia biology Chemistry Organic Chemistry Myeloid leukemia yeast asparaginase General Medicine biology.organism_classification medicine.disease Recombinant Proteins In vitro Computer Science Applications Biochemistry Drug Design Liposomes Saccharomycetales enzymatic therapy Drug Screening Assays Antitumor K562 Cells K562 cells |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 11120, p 11120 (2021) International Journal of Molecular Sciences Volume 22 Issue 20 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | The bacterial enzyme asparaginase is the main treatment option for acute lymphoblastic leukemia. However, it causes side effects, such as immunological reactions, and presents undesirable glutaminase activity. As an alternative, we have been studying asparaginase II from Saccharomyces cerevisiae, coded by ASP3 gene, which was cloned and expressed in Pichia pastoris. The recombinant asparaginase (ASP) presented antileukemic activity and a glutaminase activity 100 times lower in comparison to its asparaginase activity. In this work, we describe the development of a delivery system for ASP via its covalent attachment to functionalized polyethylene glycol (PEG) polymer chains in the outer surface of liposomes (ASP-enzymosomes). This new delivery system demonstrated antiproliferative activity against K562 (chronic myeloid leukemia) and Jurkat (acute lymphocytic leukemia) cell lines similar to that of ASP. The antiproliferative response of the ASP-enzymosomes against the Jurkat cells suggests equivalence to that of the free Escherichia coli commercial asparaginase (Aginasa®). Moreover, the ASP-enzymosomes were stable at 4 °C with no significant loss of activity within 4 days and retained 82% activity up to 37 days. Therefore, ASP-enzymosomes are a promising antileukemic drug. |
| Databáze: | OpenAIRE |
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